EMPA Acute Heart Failure

Effect of Empagliflozin on Cardiac Output in Patients With Acute Heart Failure (EMPA Acute Heart Failure)

In this study the investigators are aiming to treat patients with acute heart failure with or without diabetes with Empagliflozin or placebo. Given the beneficial effects of Empagliflozin on heart failure hospitalization in the EMPA-REG OUTCOME trial, the investigators do expect a similar beneficial effect to be present in patients with acute heart failure. Acute heart failure is a state of hydropic decompensation resulting in dyspnea and congestions, caused by different etiologies of cardiac disease. Recompensation is reached by application of diuretic drugs and fluid restriction.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 2; Acute Heart Failure
• Intervention / Treatment: Drug: Empagliflozin; Drug: Placebo

Detailed Description

In the present study patients will be randomized into 2 groups (standard of care + Empagliflozin 10 mg/d or standard of care + placebo). Cardiac output will be assessed by a medical device for noninvasive monitoring of hemodynamic parameters (cardiac output, systemic vascular resistance, stroke volume and blood pressure) using finger cuff technology for pulse contour analysis.

These investigations will inform about Empagliflozin dependent effects on hemodynamic and cardiac function in patients with acute heart failure. The investigation will further assess the therapeutic efficacy of Empagliflozin on heart failure symptoms using objective (respiratory rate, oxygen requirement, peak expiratory flow rate, urinary volume, body weight, diuretic requirement, length of hospital stay) and well accepted, patient orientated secondary endpoints. In addition, metabolic regulators and parameters relevant for cardiac function and substrate metabolism will be assessed to further investigate possible mechanisms of Empagliflozin-dependent actions on cardiac function.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • NRW
    • Aachen, NRW, Germany, 52074
      • Department of Internal Medicine I RWTH Aachen University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Patients with acute heart failure with associated signs or symptoms (dyspnea on exertion, orthopnea, paroxysmal dyspnea, peripheral oedema, chest x-ray with pulmonary congestion)
3. Serum levels of NT-proBNP ≥ 1000 pg/ml within 48 hours of Informed Consent
4. Written informed consent prior to study participation

Exclusion Criteria:

1. Type 1 diabetes
2. Participants of child-bearing age without adequate contraception
3. Pregnancy or lactating females
4. Cardiogenic shock
5. Acute coronary syndrome within 30 days prior to randomization
6. Planned or recent percutaneous or surgical coronary intervention within 30 days prior to randomization
7. Signs of ketoacidosis and/or hyperosmolar hyperglycemic syndrome (pH ≤ 7.30 and glucose >14 mmol/l and HCO3- ≤ 18 mmol/l)
8. Signs of uncontrolled active infection
9. Dyspnea due to non-cardiac causes (severe pulmonary disease, anemia, severe obesity), non-HF causes such as acute or chronic respiratory disorders
10. Coronary artery disease with requirement for revascularization within the study period
11. Renal impairment (GFR < 20 ml/min/1,73 m2)
12. Known hepatic impairment (as evidenced by total bilirubin >3 mg/dL) or history of cirrhosis with evidence of portal hypertension (e.g., presence of esophageal varices)
13. Uncontrolled thyroid disease
14. Endocrinopathies like Graves' disease, acromegaly, Cushings' disease
15. Hypertensive retinopathy or encephalopathy
16. Bariatric surgery in last 2 years prior to randomization
17. Patients in whom study participation is not deemed appropriate under consideration of clinical wellbeing by the principal investigator
18. The subject is mentally or legally incapacitated
19. The subject received an investigational drug within 30 days prior to inclusion into this study
20. Urinary tract infections or significant formation of residual urine in medical history
21. Patients with particular risk for ketoacidosis (alcohol abuse, pancreatitis, pancreatic insulin deficiency from any cause, caloric restriction etc.) or ketoacidosis in the past
22. Frequent hypoglycaemic events (in the opinion of the investigator)
23. Intolerance to Empagliflozin and excipients in Empagliflozin or rather placebo
24. Patients with severe stenosis or regurgitation of the aortic, pulmonary or mitral valve

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Empagliflozin; Patients will receive empagliflozin 10 mg qd for a period of 30 days.	Drug: Empagliflozin; Standard of Care + Empagliflozin: 10 mg (tablets) once daily; Other Names: Jardiance
PLACEBO_COMPARATOR: Placebo; Patients of the placebo arm will receive placebo tablets qd for a period of 30 days.	Drug: Placebo; Standard of Care + Placebo: Matching Placebo (tablets) once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
effect of Empagliflozin 10mg qd versus placebo on cardiac output in patients with acute heart failure	by ClearSight System	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamics	Systemic vascular resistance (mmHg⋅min⋅mL-1)	30 days
Hemodynamics	Stroke volume (ml/beat)	30 days
Exercise Capacity	Hand grip	30 days
Cardio vascular	blood pressure (mmHg)	30 days
Effect of Empagliflozin on systemic quality of life	Quality of life questionnaire	30 days
Effect of Empagliflozin on hospitalization due to cardiovascular causes or readmission for heart failure or renal failure	length of initial hospital stay	30 days
Effect of Empagliflozin on death due to cardiovascular causes	days alive and out of hospital	30 days
Urine	24 h sodium excretion (mmol/day)	30 days
Body weight	body weight (kg)	30 days
Cardio vascular	24 h heart rate (bpm)	30 days
Blood	NT-proBNP (ng/l)	30 days
Blood	cystatin C(mg/dl)	30 days
Blood	serum levels of Glucose, Glucagon, Insulin, Total-Ketone bodies, Hydroxybutyrate, Aldosterone, Free fatty acidy (mg/dl)	30 days
Blood	Hemoglobin, Haematocrit, Erythropoietin	30 days
Respiratory rate	breaths/min	30 days
Diuretic response	Δ weight kg/[(total i.v. dose)/40mg]+[(total oral dose)/80mg)] furosemide	30 days
Kidney injury risk score	by NephroCheck® (defined by TIMP-2 x IGFBP7 in urine)	30 days
change of microbiome	stool sample	30 days
Patient-reported dyspnea	visual analogue scale (VAS), 7 point categorical Likert scale	30 days
Peak expiratory flow rate		30 days
Oxygen	Saturation (%)	30 days
Oxygen	delivered (l/min)	30 days
Clinical judged diuretic requirement		30 days
Blood	eGFR	30 days
Blood	Lactate, pH, HCO3-	30 days
Blood	Serum osmolarity, Potassium, Chloride	30 days
Effect of Empagliflozin 10 mg daily on Left ventricular systolic function	ejection fraction	30 days
Effect of Empagliflozin 10 mg daily on Left ventricular diastolic function	2D and 3D parameter global strain rate E by echocardiography and by standardized parameter E/E' and left atrial (LA) volume	30 days

Collaborators and Investigators

• Sponsor: RWTH Aachen University
• Collaborators: Boehringer Ingelheim

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 11, 2018
• Primary Completion (ACTUAL): October 29, 2020
• Study Completion (ACTUAL): October 29, 2020

Study Registration Dates

• First Submitted: May 17, 2018
• First Submitted That Met QC Criteria: May 30, 2018
• First Posted (ACTUAL): June 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 27, 2022
• Last Update Submitted That Met QC Criteria: October 25, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: exercise capacity; Empagliflozin; acute heart failure; cardiac output; left ventricular systolic and diastolic function
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Heart Failure; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: 15-156; 2017-002695-45 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No